SB 225002 is a potent and selective CXCR2 chemokine receptor antagonist with IC50 value of 22nM [1].
CXCR2 is a member of the G-protein-coupled receptor family, which is responsible for neutrophil chemotaxis and margination induced by IL-8 [1].
SB 225002 is a potent and selective non-peptide inhibitor of CXCR2. It prevented IL-8 binding to CXCR2 with IC50 value of 22 nM and showed >150-fold selectivity over CXCR1. In HL60 cells, SB 225002 potently prevented IL-8 and GROa-induced neutrophil chemotaxis [1]. In CDDP-resistant and -sensitive OVCA cell lines, SB225002 induced apoptosis in both wild-type and p53-deficient cells in a p53-independent way and promoted mitotic catastrophe [2].
In rabbits, SB 225002 blocked IL-8-induced neutrophil margination [1]. In experimental colitis mice induced by TNBS, SB225002 reduced neutrophil influx, IL-1 , MIP-2, and keratinocyte-derived chemokine (KC) levels, MPO activity and the expression of vascular endothelial growth factor. While, levels of IL-4 and IL-10 were increased significantly in the colons of mice [3].
References:
[1]. White JR, Lee JM, Young PR, et al. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem, 1998, 273(17): 10095-10098.
[2]. Du M, Qiu Q, Gruslin A, et al. SB225002 promotes mitotic catastrophe in chemo-sensitive and -resistant ovarian cancer cells independent of p53 status in vitro. PLoS One, 2013, 8(1): e54572.
[3]. Manjavachi MN, Quintão NL, Campos MM, et al. The effects of the selective and non-peptide CXCR2 receptor antagonist SB225002 on acute and long-lasting models of nociception in mice. Eur J Pain, 2010, 14(1): 23-31.